Efficacy and Safety Study for an Oral Contraceptive Containing Folate

• ClinicalTrials.gov Identifier: NCT00468481
• Recruitment Status: Completed
• First Posted: May 2, 2007
• Results First Posted: January 25, 2011
• Last Update Posted: April 23, 2014
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

The purpose of this study is to determine whether the study drug is safe and effective

Condition or disease	Intervention/treatment	Phase
Neural Tube Defects; Contraception; Oral Contraceptives (OC)	Drug: Drospirenone/Ethinylestradiol/Methyltetrahydrofolate; Drug: Drospirenone/Ethinylestradiol (Yaz)	Phase 3

Detailed Description:

Acronym is used in result section: suspected/diagnosed (susp/diag)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 385 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Multi-Center, Randomized, Double-Blind Active-Controlled, Parallel Group Study to Investigate Plasma Folate, Red Blood Cell Folate and Homocysteine Levels During a 24 Week Oral Administration of an OC Containing Folate Compared to OC Alone
• Study Start Date: April 2007
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: September 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF); 1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks	Drug: Drospirenone/Ethinylestradiol/Methyltetrahydrofolate; 0.020 mg ethinylestradiol with 3.0 mg drospirenone and 0.451 mg L-5-methyltetrahydrofolate (L-5-MTHF)
Active Comparator: Drospirenone (DRSP)/Ethinylestradiol (EE); 1 tablet 0.020 mg EE/3.0 mg DRSP [YAZ] given orally/daily for 24 days followed by 1 placebo tablet given orally/daily for 4 days over a time period of 24 weeks	Drug: Drospirenone/Ethinylestradiol (Yaz); 0.020 mg ethinylestradiol with 3.0 mg drospirenone

Outcome Measures

Primary Outcome Measures :

1. Red Blood Cell (RBC) Folate Level at 24 Weeks [ Time Frame: Week 24 ]
   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
2. Plasma Folate Level at 24 Weeks [ Time Frame: Week 24 ]
   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.

Secondary Outcome Measures :

1. Mean Neural Tube Defect (NTD) Risk Reduction at Week 24 [ Time Frame: Baseline and week 24 ]
   The mean NTD risk reduction evaluated as the change from Baseline to Week 24 in NTD risk based on the formula of Daly et al (J Amer Med Assoc 1995;274(21):1698-702); NTD risk=exp (1.6463-1.2193 x natural log [RBC folate]) where natural log [RBC folate] is the natural log of RBC folate measured in nmol/L; Change from Baseline to Week 24 in NTD risk=NTD risk at Week 24 - NTD risk at Baseline
2. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4 [ Time Frame: baseline and up to week 4 ]
   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
3. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8 [ Time Frame: baseline and up to week 8 ]
   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
4. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12 [ Time Frame: baseline and up to week 12 ]
   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
5. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16 [ Time Frame: baseline and up to week 16 ]
   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
6. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20 [ Time Frame: baseline and up to week 20 ]
   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
7. Mean Change From Baseline in Plasma Folate Levels at Week 4 [ Time Frame: baseline and up to week 4 ]
   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
8. Mean Change From Baseline in Plasma Folate Levels at Week 8 [ Time Frame: baseline and up to week 8 ]
   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
9. Mean Change From Baseline in Plasma Folate Levels at Week 12 [ Time Frame: baseline and up to week 12 ]
   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
10. Mean Change From Baseline in Plasma Folate Levels at Week 16 [ Time Frame: baseline and up to week 16 ]
    Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
11. Mean Change From Baseline in Plasma Folate Levels at Week 20 [ Time Frame: baseline and up to week 20 ]
    Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
12. Mean Change From Baseline in Plasma Homocysteine Levels at Week 4 [ Time Frame: baseline and up to week 4 ]
    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
13. Mean Change From Baseline in Plasma Homocysteine Levels at Week 8 [ Time Frame: baseline and up to week 8 ]
    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
14. Mean Change From Baseline in Plasma Homocysteine Levels at Week 12 [ Time Frame: baseline and up to week 12 ]
    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
15. Mean Change From Baseline in Plasma Homocysteine Levels at Week 16 [ Time Frame: baseline and up to week 16 ]
    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
16. Mean Change From Baseline in Plasma Homocysteine Levels at Week 20 [ Time Frame: baseline and up to week 20 ]
    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
17. Mean Change From Baseline in Plasma Homocysteine Levels at Week 24 [ Time Frame: baseline and up to week 24 ]
    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

- Healthy women between 18 and 40 requesting oral contraception

Exclusion Criteria:

- The use of steroidal oral contraceptives, or any drug that could alter Oral Contraception metabolism will be prohibited during the study

Contacts and Locations

Locations

United States, California

Orange County Clinical Trials

Anaheim, California, United States, 92801

Medical Center for Clinical Research

San Diego, California, United States, 92108

United States, Maryland

SNBL Clinical Pharmacology Center, Inc.

Baltimore, Maryland, United States, 21201

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

AAIPharma, Inc.

Morrisville, North Carolina, United States, 27560

Lyndhurst Gynecologic Associates

Winston-Salem, North Carolina, United States, 27103

United States, South Carolina

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, United States, 29464

United States, Tennessee

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States, 37920

United States, Washington

NorthWest Kinetics

Tacoma, Washington, United States, 98418

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Publications of Results:

Bart S Sr, Marr J, Diefenbach K, Trummer D, Sampson-Landers C. Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study. Contraception. 2012 Jan;85(1):42-50. doi: 10.1016/j.contraception.2011.05.013. Epub 2011 Jul 13.

Castaño PM, Aydemir A, Sampson-Landers C, Lynen R. The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: dietary and blood assessments. Public Health Nutr. 2014 Jun;17(6):1375-83. doi: 10.1017/S1368980013000864. Epub 2013 Mar 27.

Taylor TN, Farkouh RA, Graham JB, Colligs A, Lindemann M, Lynen R, Candrilli SD. Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States. Am J Obstet Gynecol. 2011 Nov;205(5):460.e1-8. doi: 10.1016/j.ajog.2011.06.048. Epub 2011 Jun 21.

Campone M, Berton-Rigaud D, Joly-Lobbedez F, Baurain JF, Rolland F, Stenzl A, Fabbro M, van Dijk M, Pinkert J, Schmelter T, de Bont N, Pautier P. A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy. Oncologist. 2013;18(11):1190-1. doi: 10.1634/theoncologist.2013-0061. Epub 2013 Oct 8.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00468481
• Other Study ID Numbers: 91523; 310662 ( Other Identifier: Company internal )
• First Posted: May 2, 2007
• Results First Posted: January 25, 2011
• Last Update Posted: April 23, 2014
• Last Verified: April 2014

Keywords provided by Bayer:

Healthy women requesting contraception; Folic Acid

Additional relevant MeSH terms:

Neural Tube Defects; Spinal Dysraphism; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Drospirenone; Ethinyl Estradiol; Drospirenone and ethinyl estradiol combination; Contraceptives, Oral, Hormonal; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Hormone Antagonists; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents